Viral infections are a significant medical problem. Various antiviral treatments are available but they generally are directed to interrupting the replicating cycle of the virus. Thus, a particularly difficult problem is latent viral infection, as there is no effective treatment to eradicate the virus from host cells. Since latent infection can evade immune surveillance and reactivate the lytic cycle at any time, there is a persistent risk throughout the life. The majority of antiviral drug development has been focused on protein targets and such approaches have not been successful in eradicating the virus.
One example of a latent viral infection that is a particular problem is the herpesviridae virus family. Herpes is one of the most widespread human pathogens, with more than 90% of adults having been infected with at least one of the eight subtypes of herpes viruse. Latent infection persists in most people; and about 16% of Americans between the ages of 14 and 49 are infected with genital herpes, making it one of the most common sexually transmitted diseases. Due to latency, there is no cure for genital herpes or for herpes simplex virus type 2 (HSV-2). Once infected, a host carries the herpes virus indefinitely, even when not expressing symptoms. Similarly, human papillomavirus, or HPV is a common virus in the human population, where more than 75% of women and men will have this type of infection at one point in their life. High-risk oncogenic HPV types are able to integrate into the DNA of the cell that can result in cancer, specifically cervical cancer. Similar to the herpesviridae virus family, HPV may remain latent.
The Epstein-Barr virus (EBV), also called human herpesvirus 4 (HHV-4) is another common virus in humans. Epstein-Barr is known as the cause of infectious mononucleosis (glandular fever), and is also associated with particular forms of cancer, such as Hodgkin's lymphoma, Burkitt's lymphoma, nasopharyngeal carcinoma, and conditions associated with human immunodeficiency virus (HIV) such as hairy leukoplakia and central nervous system lymphomas. There is evidence that infection with the virus is associated with a higher risk of certain autoimmune diseases, especially dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, and multiple sclerosis. During latency, the EBV genome circularizes and resides in the cell nucleus as episomes. To date, however, no EBV vaccine or treatment exists.
Viruses, such as the herpesviridae virus family, including EBV, and HPV have the ability to lie dormant within a cell indefinitely and not be fully eradicated even after treatment. The result is that the virus can reactivate and begin producing large amounts of viral progeny without the host being infected by any new outside virus. In the latent state, the viral genome persists within the host cells as episomes; stabilized and floating in the cytoplasm or nucleus. For these latent viruses, it has not been possible to find therapeutic approaches which completely eradicate such infections.